Effect of Chronic Kidney Disease on Taste Function: A Case Control Study among Nigerian

Abstract

Taste dysfunction has been associated with chronic kidney disease (CKD) especially end stage kidney disease (ESKD) and also implicated as one of the predisposing factors for the prevalent malnutrition, muscle wasting and impaired quality of life among patients with CKD. To assess the taste function and determine the pattern of taste dysfunction in patients with CKD attending the University College Hospital, Ibadan. This was a cross sectional, hospital-based case–control study of adult patients with CKD. The control group were age and sex matched without CKD. Interviewer-assisted questionnaires were administered on all participants to obtain clinical information concerning demographics, clinical data on kidney disease and taste dysfunction. The four basic taste modalities namely; sweet, sour, bitter and salt taste senses of the participants were tested with validated “taste strips”. There were 100 patients with CKD and 100 healthy controls, age ranges between 19 and 86 years (mean ± SD = 46.3 ± 13.9 years) and 20 and 85 years (mean ± SD = 43.4 ± 14.9 years), respectively. There was no statistically significant difference between cases and control gender distribution (p = 0.57). Hypogeusia was found in 27.0% of CKD patients with specific taste modalities dysfunction for salt, sour, sweet and bitter taste of 13.0, 24.0, 13.0 and 17.0%, respectively. The controls only had specific taste modalities dysfunction for salt, sour and bitter taste of 1.0% for each of the taste modalities. The mean total taste scores in the cases and controls were − 9.8 ± 3.2 and 13.4 ± 1.5 (p = 0.001), respectively. The mean taste scores were significantly lower among the cases than controls, salt taste-2.82 ± 1.1 and 3.7 ± 0.7 (p = 0.001), sour taste − 2.2 ± 1.0 and 3.2 ± 0.7 (p = 0.001), sweet taste-, 2.9 ± 1.8 and 3.8 ± 0.5 (p = 0.001), bitter taste − 1.9 ± 1.2 and 2.8 ± 0.9 (p = 0.001). Taste dysfunction is prevalent among patients with CKD and the affectation involves all taste modalities.

Introduction

Chronic kidney disease (CKD) affects the function of almost all the systems in the body including the gastrointestinal tract which is responsible for ingestion, digestion, absorption and excretion of food materials.

Taste is very important in nutrition; it affects the willingness (desire) to eat and determines the quantity of food that is eaten. Appreciation of taste is one of the factors that gives satisfaction derived from eating. Taste disorder has been reported among CKD patients but it is unclear whether it is a primary or secondary disorder [1]. Inadequate food intake due to taste disorder has been implicated as one of the predisposing factors to malnutrition muscle wasting and poor outcomes among patients with CKD [1].

The survival rate among patients with CKD has improved over the years due to advancement in health care delivery and improved man power [2]. With improved healthcare and patients’ survival, these patients are now showing concern about other morbidities including taste disorders, hence the need for researchers to pay attention and investigate appropriately. Patients with CKD have been reported to suffer from taste dysfunction [3, 4, 5], mechanisms postulated for this taste dysfunction include; dry mouth, tongue coating, mucosal inflammation, or oral ulceration which have been reported in CKD patients [6] might have contributed to taste disorder in them. Uraemic state affecting the taste bud prevent its regeneration and affects the nerve supply to the taste bud. Others causes of impaired taste include medication usage, changes in salivary composition, differences in dietary intake and nutritional status, including zinc deficiency [3, 4, 5, 7, 8]. Taste dysfunction in patients with CKD is also regarded as an adaptive mechanism for the survival of a failing kidney by limiting its exposure to various metabolite from diet, that may stress the kidney beyond its capacity thereby hasting its complete shutdown [4]. This has been explained by the loss of taste for umami thereby reducing intake of animal protein which is a protective form of adaptation to the failing kidney [4].

Disorder of taste as a complication of CKD is often not factored into the management of the patients especially in developing nations. Hence, there is a need to determine the prevalence, and pattern of taste disorder in CKD patients to provide holistic management towards better treatment outcomes and improved quality of life. Therefore, this study aimed to assess the taste function to determining the prevalence and pattern of taste dysfunction among patients with CKD.

Method

This was a hospital-based case–control study conducted at the Medical Outpatient (MOP) clinic, medical wards and Ear Nose and Throat (ENT) clinic of the University College Hospital, Ibadan.

Consenting adult patients (≥ 18 years) with clinical and laboratory diagnosis of CKD defined as estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m² with or without albuminuria. While the controls were healthy volunteers, who were age and gender matched individuals with no clinical or laboratory evidence of CKD. Excluded from the study were individuals with known taste dysfunction from childhood, those with diabetes mellitus, known thyroid hormone disorder, known dysfunction of smell, those suffering from Chronic Suppurative Otitis Media (CSOM), previous history of Smoking or current smoker and those with previous history of surgery or trauma to the tongue.

Written informed consent was obtained and interviewer’s assisted questionnaire was administered on all participants to collect biodata, relevant clinical data on symptoms and signs of kidney disease, taste disorder, lifestyles, medication history, medical and surgical history. Blood samples were collected to determine serum creatinine which was used to calculate the estimated Glomerular Filtration (eGFR) of each participant. Height and weight of the participants were measured and body mass index (BMI) was calculated. The taste function was assessed with standard taste strips (Burghart, Wedel, Germany) which have been previously validated and used for the assessment of taste function among Nigerian population [9].

The strips contained four basic taste (sweet, sour, salty, bitter) each in 4 different concentrations, impregnated at one end with 0.05, 0.1, 0.2, or 0.4 g/mL of sucrose (sweet taste); 0.05, 0.09, 0.165, or 0.3 g/mL of citric acid (sour taste); 0.016, 0.04, 0.1, or 0.25 g/mL of sodium chloride (salty taste); or 0.0004, 0.0009, 0.0024, or 0.006 g/mL of quinine hydrochloride (bitter taste) in increasing order. Plain strips with no tastants impregnated in them, were also used to determine the possibility of phantogeusia or patients confabulating. [10] The strips were placed in the center of the anterior two-third of the extended tongue at about 1.5 cm from the tip of the tongue and participants were then asked to close their mouth for whole mouth testing in a total of 18 trials. Before each administration of a strip, the mouth was rinsed with water. The tastes were presented in order of increasing concentrations, starting with the lowest concentration until patient could appreciate the taste or fails to appreciate it in the strips with highest concentration for each of the taste modalities and they were scored appropriately; no score was allotted to the blank strips.

Each of the two sequences of eighteen taste strips (four concentrations of each taste quality plus two blanks) were applied in a pseudo-randomized order. While closing the mouth over the taste strip and with or without tongue movement within the closed mouth patients were asked to identify the taste from a list of five descriptors, i.e., sweet, sour, salty, bitter and no taste (multiple forced- choice). Gustatory function was obtained by the number of correctly identified taste added up to a “taste score” [10, 11], lowest concentration was 4 points, the highest concentration was 1 point, while failure to appreciate strips with highest concentration was 0. Therefore, minimum score of 0 and maximum of 16 could be obtained and the whole testing procedure for the 4 tastants required about 30 min.

Statistical Analysis

Data obtained were entered and analysed using statistical package (IBM-SPSS statistic, version 22). Demographic variables were represented using tables and charts while summary statistics were done using means and proportions. The qualitative socio-demographic characteristics of patients with CKD and healthy controls were compared using Chi-square tests. The comparison of mean taste scores between patients with CKD and healthy controls was done using the independent samples t-test. The eGFR was graded as stage 1 CKD ≥ 90, stage 2 CKD 60–89, stage 3 CKD 30–59, stage 4 CKD 15–29, stage 5 CKD (end stage kidney disease [ESKD]) < 15. BMI were calculated using this equation for BMI [12], BMI = Weight (kg)/Height (m)² which applies equally to men and women. BMI were categorized [12]; underweight =  < 18.5, normal = 18.5–24.9, overweight = 25.0–29.9, obesity = 30.0  ≥ 40. While taste was graded as taste score normal values defined as “taste strip” scores above the 10th percentile of a group of healthy population [10]. Normogeusia was total taste score ≥ 9, hypogeusia was < 9 while ageusia was 0. Normogeusia for salt, sour and sweet was taste score ≥ 2 while for bitter, normogeusia was taste score ≥ 1. Hypogeusia was taste score of 1 or false identification for salt, sour and sweet but only false identification for bitter. Ageusia was 0 for all taste modalities [10].

Statistical significant were set at 0.05 for variable comparisons.

Result

There were 100 subjects with CKD and 100 age and gender matched healthy controls. The age ranged between 19–86 and 20–85 years, respectively while the mean age (SD) were 46.3 (13.9) and 43.4 (14.9) years, respectively, Table 1. There were 56 males 44 females among the cases, while the control had 52 males and 48 females. There was no statistically significant difference between cases and control gender distribution (p = 0.57). The mean weight of cases; 64.6 ± 12.6 kg was significantly lower than that of the control 70.7 ± 13.2 kg (p = 0.001). Similarly, the mean body mass index of cases; 23.4 ± 4.7 kg/m² was significantly lower than that of the controls; 25.1 ± 4.5 kg/m² (p = 0.009). The mean height of the cases and controls were the same 1.7 ± 0.8 m. The mean BMI of both groups however were within normal range although there were more underweight participants among the cases than the controls Table 1.

Table 1.

Socio-demographic and clinical characteristics of participants

Continuous variables	Case mean (SD) n = 100	Control mean (SD) n = 100	t-Test	p-Value
Age (years)	46.3 (13.9)	43.4 (14.9)	1.414	0.159
Age range (years)	19–86	20–85
Mean eGFR (ml/min/1.73 m2)	23.7	122.8	20.848	0.001
Weight (kg)	64.6 (12.6)	70.7 (13.2)	− 3.369	0.001
Height (m)	1.7 (0.08)	1.7 (0.07)	− 1.455	0.147
Body mass index (kg/m2)	23.4 (4.7)	25.1 (4.5)	− 2.649	0.009
Demographic-data for categorical data			χ2 Test	p-Value
Sex	N (%)	N (%)	0.322	0.570
Male (n = 108)	56 (56.0)	52 (52.0)
Female (n = 92)	44 (44.0)	48 (48.0)
Body mass index (BMI)			12.341	0.006
Underweight	9 (9.0)	1 (1.0)
Normal	66 (66.0)	56 (56.0)
Overweight	15 (15.0)	29 (29.0)
Obesity	10 (10.0)	14 (14.0)
Taste dysfunction	27 (27.0%)	0 (0.0%)	10.099	0.001
Hypogeusia	27 (27.0%)	0 (0.0%)
Ageusia	0 (0.0%)	0 (0.0%)

The cases consisted of 4 (4%) stage 1 CKD, 8 (8%) stage 2 CKD, 19 (19%) stage 3 CKD, 22 (22%) stage 4 CKD and 47 (47%) stage 5, while all the control had eGFR ≥ 90 (normal) as shown in Fig. 1

Fig. 1.

Distribution of cases and control based on eGFR

Taste dysfunction was found in 27 (27.0%) cases, all were hypogeusia (total taste score < 9, > 0) Fig. 2. The four components of taste assessment were also analysed separately i.e. salt, sour, sweet and bitter Fig. 2.

Fig. 2.

Spectrum of taste dysfunction among cases with chronic kidney disease (total taste score i.e. the sum of the scores of each of the four taste modalities; > 9-normogeusia, < 9 > 0-hypogeusia, 0-ageusia). Pattern of gustatory test components among cases (each taste modality test grading, normogeusia was taste score ≥ 2 for salt, sour and sweet, ≥ 1 for bitter. Hypogeusia was taste score of 1 or false identification for salt, sour and sweet, only false identification for bitter. Ageusia was taste score 0 for each of the taste modalities)

The prevalence of taste dysfunction among the control was 0.0%, all had total taste score > 9 (normogeusia) despite some of them having ageusia and hypogeusia to specific taste modalities Fig. 3.

Fig. 3.

Pattern of gustatory test components among control

The mean score of taste for all the taste modalities among the cases were 2.82 ± 1.1, 2.2 ± 1.0, 2.9 ± 1.8, 1.9 ± 1.2 and 9.8 ± 3.2 for salt, sour, sweet, bitter and total taste score, respectively. While among the control, the mean scores were 3.7 ± 0.7, 3.2 ± 0.7, 3.8 ± 0.5, 2.8 ± 0.9, and 13.4 ± 1.5 for salt, sour, sweet, bitter and total taste score respectively. The mean taste scores of cases were significantly lower than in the controls in all domains (p = 0.001) Table 2.

Table 2.

Comparison of mean taste scores between cases N = 100 and control N = 100

Taste domain	Cases mean ± SD score n = 100	Control mean ± SD score n = 100	t-Test	p-Value
Salt	2.82 ± 1.1	3.7 ± .7	− 7.118	0.001
Sour	2.2 ± 1.0	3.2 ± .7	− 8.536	0.001
Sweet	2.9 ± 1.8	3.8 ± .5	− 7.073	0.001
Bitter	1.9 ± 1.2	2.8 ± .9	− 5.698	0.001
Total taste score	9.8 ± 3.2	13.4 ± 1.5	− 10.099	0.001

The duration of CKD shows significant association with taste dysfunction among CKD patients, the longer the duration of CKD, the higher the prevalence of taste dysfunction, χ² = 4.818, p = 0.028 (Table 3).

Table 3.

Duration of CKD and taste dysfunction among CKD patients

Variable	Severity of taste dysfunction			χ2 Test	p-Value
Duration of CKD (months)	Normogeusia N (%)	Hypogeusia N (%)	Total
≤ 1	22 (30.1)	3 (11.1)	25	4.815	0.028
2–6	24 (32.9)	9 (33.3)	33
7–12	8 (11.0)	2 (7.4)	10
13–24	7 (9.6)	5 (18.5)	12
> 24	12 (16.4)	8 (29.6)	20
Total	73	27	100

The relationship between stages of CKD and severity of taste dysfunction was analysed and there was no statistically significant relationship with severity of taste dysfunction, χ² = 2.589, p = 0.629 (Table 4).

Table 4.

Relationship between stages of CKD and severity of taste dysfunction among the cases (N = 100)

Severity of CKD	Severity of taste dysfunction			χ2test	p-Value
Stage of CKD	Normogeusia N (%)	Hypogeusia N (%)	Total
Stage 1 (≥ 90 normal or high)	3 (4.1)	1 (3.7)	4	2.589	0.629
Stage 2 (60–89 mildly decreased)	7 (9.6)	1 (3.7)	8
Stage 3 (30–59 moderately decreased)	15 (20.5)	4 (14.8)	19
Stage 4 (15–29 severely decreased)	17 (23.3)	5 (18.5)	22
Stage 5 (< 15 end stage)	31 (42.5)	16 (59.3)	47
Total	73	27	100

Discussion

This study has revealed prevalent taste dysfunction among CKD patients but non among the healthy control who were age and gender matched.

The cases distribution among participants showed that more than 50% of the cases had advanced stages of CKD with average eGFR of 23.7 and compared similarly to the studies by Mcmahon et al. [3] where cases were stages 3–5 CKD with average eGFR of 33.1 ± 12.7 and Kusaba et al. [8] with average eGFR of 20.9 ± 12.2 and [3, 8]. In a study by Manley et al. [4] in Australia, only CKD patients with eGFR < 25 were included in the study [4]. Although, the participants with early stages of CKD were few in this study, their inclusion gave room for comparison of taste dysfunction across all the stages of CKD.

The prevalence of gustatory dysfunction among patients with CKD in this study was 27.0%, all were hypogeusia. This gustatory dysfunction was not unconnected to the increasing duration of their CKD, even though the taste dysfunction was observed not to have any relationship with the severity of CKD, as the taste dysfunction occurred across all CKD stages.

This study, unlike the previous studies carried out in patients with CKD, it did not only determine the prevalence of taste dysfunction among them but also established the sensitivity of taste for different taste modalities among them using validated taste strips. This study also employed the use of validated taste strip, unlike the liquid tastants used by majority of the previous studies which was reported to have shortcoming of uneven dilution steps between the different tastants [13]. Mcmahon et al. [3] in a study done in Australia, where taste identification and intensity were analysed among the five taste modalities, reported that the taste dysfunction was highly prevalent among patients with CKD in the different taste modalities but did not determine the overall prevalence of taste dysfunction. Similarly, Kusaba et al. [8] reported high prevalence of elevated recognition threshold and detection threshold for salt in patient with CKD (71.0 and 39%, respectively) compared to control (27 and 18%, respectively).

In this study, patients with CKD had gustatory dysfunctions which affect all the four taste modalities while the control group had negligible taste modality dysfunction. This finding has demonstrated that taste dysfunction might contributes to the increased morbidity and poor outcome observed in patients with CKD. Furthermore, the high prevalence taste dysfunction was in all taste modalities. This further buttresses the fact that CKD effect on taste is not specific for any taste modality and therefore not connected to the mechanisms of taste stimuli sensation. This is because, the sour taste which employs direct interaction with ion channels, had the highest frequency of dysfunction, while bitter taste stimuli which binds to seven-transmembrane spanning G-protein coupled receptors had the worst severity of dysfunction. [14, 15] In this study, the worst taste modality was bitter taste because all patients with bitter taste dysfunction had ageusia to bitter taste, followed by sour taste, even though most dysfunction to sour taste were due to obtaining a result that mistaken sour for salty taste i.e. most participants that missed recognising sour taste identified it as salt taste. Sweet and salty taste had equal and less prevalence of dysfunction but varying proportion of hypogeusia and ageusia. The taste modalities dysfunction in the controls were negligible suggesting that the constituent metabolic derangement may be the culprit for various taste dysfunction in patients with CKD.

Previous studies on taste assessment among healthy population also had low prevalence of taste dysfunction. Similar to this study, Pribitkin et al. [16] found 0.85% prevalence figure despite studying a larger population of 1176 healthy people. However, 5% prevalence was reported by Hummel et al. [17] in a study of 761 healthy people. The low prevalence of taste disorder among healthy population proved that taste dysfunction is rare among healthy population. This may be due to the fact that the taste pathway has multiple neuronal pathways involved, making it less susceptible to dysfunction from minor or trivial insult unlike olfactory pathway [14, 16, 18].

The high frequency of salt and sour taste confusion found among the patients with CKD in this study was also reported among healthy population by Muellar et al. [10] However, the healthy control in this study had only one case each, of salt confused for sour and vice versa. This means that there may be some similarity in the perception of the two taste modalities, as reported in previous studies, for both taste modalities interact with ion channels [14, 15].

Similar to this study, Manley et al. [4] reported highest taste modality dysfunction in patient with CKD in the Umami taste modality (53.0%) followed by sour taste (43.0%) and then bitter taste (30.0%). This study, even though umami taste was not included, had sour taste as the highest taste modality dysfunction (24.0%), also followed by bitter taste (17.0%) in the same order, but at lower prevalence. The best taste modality reported by Manley et al. [4] was sweet taste similar to this study where sweet and salt taste were the best. The subtle differences observed between this study and Manley et al. [4] may be connected to the differences in the sample size and tastants used in the studies.

Contrary to the findings in this study, Mcmahon et al. [3] reported no significant difference in salt taste identification between CKD patients and the control, also reported salt and sour taste as least identified taste modalities among CKD compared to control. However, Mcmahon et al. [3] had less participants and unequal proportion of cases and control.

The significantly lower mean weight and mean BMI of the cases than that of the controls in this study, may be explained by the reduced food intake by the CKD patients presumably due to the prevalent taste dysfunction among other factors. This lower BMI in patients with CKD might indicate that some level of malnutrition was present and this is similar to findings from previous studies by Morais et al. [19], Griep et al. [20] and Armstrong et al. [21] All the three studies used BMI as an indirect measure of nutritional status in CKD patients [19, 20, 21]. Therefore, it is imperative that nutritional assessment is incorporated into the routine evaluation of patients with CKD. The prompt detection and treatment of taste dysfunction offers the hope of adequate nutritional rehabilitation and improved outcomes among patients with CKD.

The limitations of the study included inability to recruit equal proportion of CKD stages because most of patients seen at the hospital were those in advanced stages of CKD. Although, the cases and controls were age and gender matched, the weight was not matched, and this makes it impossible to eliminate malnutrition as a factor for taste dysfunction among the CKD patients.

Conclusion

This study has revealed high prevalence of taste dysfunction among CKD patients and the taste dysfunction is not specific for a particular taste modality. This finding will serve as basis to ensure taste function assessment is included as parts of routine evaluation of patients with CKD, with the aim of improving their nutritional status and quality of life.